A transcriptome-wide association study of 229,000 women identifies new candidate susceptibility genes for breast cancer

© 2018 The Author(s) The breast cancer risk variants identified in genome-wide association studies explain only a small fraction of the familial relative risk, and the genes responsible for these associations remain largely unknown. To identify novel risk loci and likely causal genes, we performed a...

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Main Authors:	Wu, L., Shi, W., Long, J., Guo, X., Michailidou, K., Beesley, J., Bolla, M., Shu, X., Lu, Y., Cai, Q., Al-Ejeh, F., Rozali, E., Wang, Q., Dennis, J., Li, B., Zeng, C., Feng, H., Gusev, A., Barfield, R., Andrulis, I., Anton-Culver, H., Arndt, V., Aronson, K., Auer, P., Barrdahl, M., Baynes, C., Beckmann, M., Benitez, J., Bermisheva, M., Blomqvist, C., Bogdanova, N., Bojesen, S., Brauch, H., Brenner, H., Brinton, L., Broberg, P., Brucker, S., Burwinkel, B., Caldés, T., Canzian, F., Carter, B., Castelao, J., Chang-Claude, J., Chen, X., Cheng, T., Christiansen, H., Clarke, C., Collée, M., Cornelissen, S., Couch, F., Cox, D., Cox, A., Cross, S., Cunningham, J., Czene, K., Daly, M., Devilee, P., Doheny, K., Dörk, T., Dos-Santos-Silva, I., Dumont, M., Dwek, M., Eccles, D., Eilber, U., Eliassen, A., Engel, C., Eriksson, M., Fachal, L., Fasching, P., Figueroa, J., Flesch-Janys, D., Fletcher, O., Flyger, H., Fritschi, Lin, Gabrielson, M.
Format:	Journal Article
Published:	Nature Publishing Group 2018
Online Access:	http://hdl.handle.net/20.500.11937/68945

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author	Wu, L. Shi, W. Long, J. Guo, X. Michailidou, K. Beesley, J. Bolla, M. Shu, X. Lu, Y. Cai, Q. Al-Ejeh, F. Rozali, E. Wang, Q. Dennis, J. Li, B. Zeng, C. Feng, H. Gusev, A. Barfield, R. Andrulis, I. Anton-Culver, H. Arndt, V. Aronson, K. Auer, P. Barrdahl, M. Baynes, C. Beckmann, M. Benitez, J. Bermisheva, M. Blomqvist, C. Bogdanova, N. Bojesen, S. Brauch, H. Brenner, H. Brinton, L. Broberg, P. Brucker, S. Burwinkel, B. Caldés, T. Canzian, F. Carter, B. Castelao, J. Chang-Claude, J. Chen, X. Cheng, T. Christiansen, H. Clarke, C. Collée, M. Cornelissen, S. Couch, F. Cox, D. Cox, A. Cross, S. Cunningham, J. Czene, K. Daly, M. Devilee, P. Doheny, K. Dörk, T. Dos-Santos-Silva, I. Dumont, M. Dwek, M. Eccles, D. Eilber, U. Eliassen, A. Engel, C. Eriksson, M. Fachal, L. Fasching, P. Figueroa, J. Flesch-Janys, D. Fletcher, O. Flyger, H. Fritschi, Lin Gabrielson, M.
author_facet	Wu, L. Shi, W. Long, J. Guo, X. Michailidou, K. Beesley, J. Bolla, M. Shu, X. Lu, Y. Cai, Q. Al-Ejeh, F. Rozali, E. Wang, Q. Dennis, J. Li, B. Zeng, C. Feng, H. Gusev, A. Barfield, R. Andrulis, I. Anton-Culver, H. Arndt, V. Aronson, K. Auer, P. Barrdahl, M. Baynes, C. Beckmann, M. Benitez, J. Bermisheva, M. Blomqvist, C. Bogdanova, N. Bojesen, S. Brauch, H. Brenner, H. Brinton, L. Broberg, P. Brucker, S. Burwinkel, B. Caldés, T. Canzian, F. Carter, B. Castelao, J. Chang-Claude, J. Chen, X. Cheng, T. Christiansen, H. Clarke, C. Collée, M. Cornelissen, S. Couch, F. Cox, D. Cox, A. Cross, S. Cunningham, J. Czene, K. Daly, M. Devilee, P. Doheny, K. Dörk, T. Dos-Santos-Silva, I. Dumont, M. Dwek, M. Eccles, D. Eilber, U. Eliassen, A. Engel, C. Eriksson, M. Fachal, L. Fasching, P. Figueroa, J. Flesch-Janys, D. Fletcher, O. Flyger, H. Fritschi, Lin Gabrielson, M.
author_sort	Wu, L.
building	Curtin Institutional Repository
collection	Online Access
description	© 2018 The Author(s) The breast cancer risk variants identified in genome-wide association studies explain only a small fraction of the familial relative risk, and the genes responsible for these associations remain largely unknown. To identify novel risk loci and likely causal genes, we performed a transcriptome-wide association study evaluating associations of genetically predicted gene expression with breast cancer risk in 122,977 cases and 105,974 controls of European ancestry. We used data from the Genotype-Tissue Expression Project to establish genetic models to predict gene expression in breast tissue and evaluated model performance using data from The Cancer Genome Atlas. Of the 8,597 genes evaluated, significant associations were identified for 48 at a Bonferroni-corrected threshold of P < 5.82 × 10-6, including 14 genes at loci not yet reported for breast cancer. We silenced 13 genes and showed an effect for 11 on cell proliferation and/or colony-forming efficiency. Our study provides new insights into breast cancer genetics and biology.
first_indexed	2025-11-14T10:39:27Z
format	Journal Article
id	curtin-20.500.11937-68945
institution	Curtin University Malaysia
institution_category	Local University
last_indexed	2025-11-14T10:39:27Z
publishDate	2018
publisher	Nature Publishing Group
recordtype	eprints
repository_type	Digital Repository
spelling	curtin-20.500.11937-689452018-06-29T12:35:59Z A transcriptome-wide association study of 229,000 women identifies new candidate susceptibility genes for breast cancer Wu, L. Shi, W. Long, J. Guo, X. Michailidou, K. Beesley, J. Bolla, M. Shu, X. Lu, Y. Cai, Q. Al-Ejeh, F. Rozali, E. Wang, Q. Dennis, J. Li, B. Zeng, C. Feng, H. Gusev, A. Barfield, R. Andrulis, I. Anton-Culver, H. Arndt, V. Aronson, K. Auer, P. Barrdahl, M. Baynes, C. Beckmann, M. Benitez, J. Bermisheva, M. Blomqvist, C. Bogdanova, N. Bojesen, S. Brauch, H. Brenner, H. Brinton, L. Broberg, P. Brucker, S. Burwinkel, B. Caldés, T. Canzian, F. Carter, B. Castelao, J. Chang-Claude, J. Chen, X. Cheng, T. Christiansen, H. Clarke, C. Collée, M. Cornelissen, S. Couch, F. Cox, D. Cox, A. Cross, S. Cunningham, J. Czene, K. Daly, M. Devilee, P. Doheny, K. Dörk, T. Dos-Santos-Silva, I. Dumont, M. Dwek, M. Eccles, D. Eilber, U. Eliassen, A. Engel, C. Eriksson, M. Fachal, L. Fasching, P. Figueroa, J. Flesch-Janys, D. Fletcher, O. Flyger, H. Fritschi, Lin Gabrielson, M. © 2018 The Author(s) The breast cancer risk variants identified in genome-wide association studies explain only a small fraction of the familial relative risk, and the genes responsible for these associations remain largely unknown. To identify novel risk loci and likely causal genes, we performed a transcriptome-wide association study evaluating associations of genetically predicted gene expression with breast cancer risk in 122,977 cases and 105,974 controls of European ancestry. We used data from the Genotype-Tissue Expression Project to establish genetic models to predict gene expression in breast tissue and evaluated model performance using data from The Cancer Genome Atlas. Of the 8,597 genes evaluated, significant associations were identified for 48 at a Bonferroni-corrected threshold of P < 5.82 × 10-6, including 14 genes at loci not yet reported for breast cancer. We silenced 13 genes and showed an effect for 11 on cell proliferation and/or colony-forming efficiency. Our study provides new insights into breast cancer genetics and biology. 2018 Journal Article http://hdl.handle.net/20.500.11937/68945 10.1038/s41588-018-0132-x Nature Publishing Group restricted
spellingShingle	Wu, L. Shi, W. Long, J. Guo, X. Michailidou, K. Beesley, J. Bolla, M. Shu, X. Lu, Y. Cai, Q. Al-Ejeh, F. Rozali, E. Wang, Q. Dennis, J. Li, B. Zeng, C. Feng, H. Gusev, A. Barfield, R. Andrulis, I. Anton-Culver, H. Arndt, V. Aronson, K. Auer, P. Barrdahl, M. Baynes, C. Beckmann, M. Benitez, J. Bermisheva, M. Blomqvist, C. Bogdanova, N. Bojesen, S. Brauch, H. Brenner, H. Brinton, L. Broberg, P. Brucker, S. Burwinkel, B. Caldés, T. Canzian, F. Carter, B. Castelao, J. Chang-Claude, J. Chen, X. Cheng, T. Christiansen, H. Clarke, C. Collée, M. Cornelissen, S. Couch, F. Cox, D. Cox, A. Cross, S. Cunningham, J. Czene, K. Daly, M. Devilee, P. Doheny, K. Dörk, T. Dos-Santos-Silva, I. Dumont, M. Dwek, M. Eccles, D. Eilber, U. Eliassen, A. Engel, C. Eriksson, M. Fachal, L. Fasching, P. Figueroa, J. Flesch-Janys, D. Fletcher, O. Flyger, H. Fritschi, Lin Gabrielson, M. A transcriptome-wide association study of 229,000 women identifies new candidate susceptibility genes for breast cancer
title	A transcriptome-wide association study of 229,000 women identifies new candidate susceptibility genes for breast cancer
title_full	A transcriptome-wide association study of 229,000 women identifies new candidate susceptibility genes for breast cancer
title_fullStr	A transcriptome-wide association study of 229,000 women identifies new candidate susceptibility genes for breast cancer
title_full_unstemmed	A transcriptome-wide association study of 229,000 women identifies new candidate susceptibility genes for breast cancer
title_short	A transcriptome-wide association study of 229,000 women identifies new candidate susceptibility genes for breast cancer
title_sort	transcriptome-wide association study of 229,000 women identifies new candidate susceptibility genes for breast cancer
url	http://hdl.handle.net/20.500.11937/68945

A transcriptome-wide association study of 229,000 women identifies new candidate susceptibility genes for breast cancer

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